First Time Use of SD-809 in Huntington Disease (First-HD)

A Randomized Double-Blind, Placebo-Controlled Study of SD-809 Extended Release for the Treatment of Chorea Associated With Huntington Disease

The purpose of this study is to determine whether SD-809 tablets are effective in the treatment of chorea associated with Huntington's Disease.

Study Overview

• Status: Completed
• Conditions: Chorea
• Intervention / Treatment: Drug: SD-809; Drug: Placebo

Detailed Description

This is a randomized, double-blind, placebo-controlled, parallel-group study designed to evaluate the efficacy, safety and tolerability of SD-809 for the treatment of chorea associated with Huntington's Disease. Approximately 90 subjects will be randomized (1:1) into the study, with approximately 45 subjects receiving SD-809 and 45 subjects receiving placebo. The study will be conducted at approximately 30 centers in the U.S. and Canada.

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Kew Vic, Australia
    • Teva Investigational Site 144
  • Sydney, Australia
    • Teva Investigational Site 054
• Canada
  • Montreal, Canada
    • Teva Investigational Site 098
  • North York, Canada
    • Teva Investigational Site 300
  • Ottawa, Canada
    • Teva Investigational Site 231
  • Ottawa, Canada
    • Teva Investigational Site 300
• United States
  • Alabama
    • Birmingham, Alabama, United States
      • Teva Investigational Site 057
  • Arizona
    • Phoenix, Arizona, United States
      • Teva Investigational Site 038
  • Arkansas
    • Fayetteville, Arkansas, United States
      • Teva Investigational Site 298
  • California
    • Los Angeles, California, United States
      • Teva Investigational Site 050
  • Colorado
    • Englewood, Colorado, United States
      • Teva Investigational Site 052
  • District of Columbia
    • Washington, D.C., District of Columbia, United States
      • Teva Investigational Site 333
  • Florida
    • Boca Raton, Florida, United States
      • Teva Investigational Site 196
    • Gainesville, Florida, United States
      • Teva Investigational Site 160
    • Miami, Florida, United States
      • Teva Investigational Site 014
  • Georgia
    • Atlanta, Georgia, United States
      • Teva Investigational Site 032
  • Indiana
    • Indianapolis, Indiana, United States
      • Teva Investigational Site 045
  • Iowa
    • Iowa City, Iowa, United States
      • Teva Investigational Site 024
  • Kansas
    • Kansas City, Kansas, United States
      • Teva Investigational Site 029
    • Wichita, Kansas, United States
      • Teva Investigational Site 083
  • Kentucky
    • Louisville, Kentucky, United States
      • Teva Investigational Site 087
  • Maryland
    • Baltimore, Maryland, United States
      • Teva Investigational Site 028
  • Massachusetts
    • Boston, Massachusetts, United States
      • Teva Investigational Site 040
  • Missouri
    • Saint Louis, Missouri, United States
      • Teva Investigational Site 027
  • Nevada
    • Las Vegas, Nevada, United States
      • Teva Investigational Site 194
  • New Jersey
    • Camden, New Jersey, United States
      • Teva Investigational Site 328
    • New Brunswick, New Jersey, United States
      • Teva Investigational Site 026
  • New York
    • Albany, New York, United States
      • Teva Investigational Site 037
    • New York, New York, United States
      • Teva Investigational Site 002
    • Patchogue, New York, United States
      • Teva Investigational Site 342
  • North Carolina
    • Durham, North Carolina, United States
      • Teva Investigational Site 119
  • Ohio
    • Cincinnati, Ohio, United States
      • Teva Investigational Site 089
    • Columbus, Ohio, United States
      • Teva Investigational Site 020
    • Toledo, Ohio, United States
      • Teva Investigational Site 093
  • Oklahoma
    • Tulsa, Oklahoma, United States
      • Teva Investigational Site 341
  • Tennessee
    • Nashville, Tennessee, United States
      • Teva Investigational Site 031
  • Texas
    • Houston, Texas, United States
      • Teva Investigational Site 007
    • Houston, Texas, United States
      • Teva Investigational Site 199
  • Utah
    • Salt Lake City, Utah, United States
      • Teva Investigational Site 100
  • Vermont
    • Burlington, Vermont, United States
      • Teva Investigational Site 137
  • Washington
    • Kirkland, Washington, United States
      • Teva Investigational Site 220
    • Seattle, Washington, United States
      • Teva Investigational Site 096
  • Wisconsin
    • Milwaukee, Wisconsin, United States
      • Teva Investigational Site 104

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject is at least 18 years of age or the age of majority (whichever is older) at Screening.
• Subject has been diagnosed with manifest HD
• Subject is able to swallow study medication whole.
• Female subjects of childbearing potential agree to use an acceptable method of contraception from screening through study completion.
• The subject has a reliable caregiver who interacts with the patient on a daily basis, oversees study drug administration, assures attendance at study visits and participates in evaluations, as required.
• Subject is able to ambulate without assistance for at least 20 yards (Note: The use of assistive devices (i.e., walker, cane) is permitted during ambulation).

Exclusion Criteria:

• Subject has a serious untreated or under-treated psychiatric illness, such as depression, at Screening or Baseline.
• Subject has active suicidal ideation at Screening or Baseline.
• Subject has history of suicidal behavior at Screening or Baseline:
• Subject has evidence for depression at Screening or Baseline.
• Subject has an unstable or serious medical or psychiatric illness at Screening or Baseline.
• Subject has been recently exposed to tetrabenazine.

• Subject has received any of the following concomitant medications within 30 days of Screening or Baseline:

  • Antipsychotics
  • Metoclopramide
  • Monoamine oxidase inhibitors (MAOI)
  • Levodopa or dopamine agonists
  • Reserpine
  • Amantadine
  • Memantine
• Subject has significantly impaired swallowing function at Screening.
• Subject has significantly impaired speaking at Screening.
• Subject requires treatment with drugs known to prolong the QT interval.
• Subject has a prolonged QT interval on 12-lead ECG at Screening.
• Subject has evidence of hepatic impairment at Screening.
• Subject has evidence of significant renal impairment at Screening.
• Subject has known allergy to any of the components of study medication.
• Subject has participated in an investigational drug or device trial within 30 days (or 5 drug half-lives) of Screening, whichever is longer.
• Subject is pregnant or breast-feeding at Screening or Baseline.
• Subject acknowledges present use of illicit drugs at Screening.
• Subject has a history of alcohol or substance abuse in the previous 12 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SD-809 ER Tablets; SD-809 ER tablets are available in three dose strengths: 6, 9 and 12 mg, all of which are identical in size, shape and color (white). All are administered three times a day, with the 6 mg final dose is placebo.	Drug: SD-809; SD-809 tablets are available in three dose strengths: 6, 9 and 12 mg, all of which are identical in size, shape and color (white).; Other Names: deutetrabenazine; Drug: Placebo; Placebo tablets are identical in appearance to SD-809 tablets.
Experimental: SD-809 Tablets; SD-809 tablets are available in three dose strengths: 6, 9 and 12 mg, all of which are identical in size, shape and color (white). All are administered three times a day, with the 6 mg final dose is placebo.	Drug: SD-809; SD-809 tablets are available in three dose strengths: 6, 9 and 12 mg, all of which are identical in size, shape and color (white).; Other Names: deutetrabenazine; Drug: Placebo; Placebo tablets are identical in appearance to SD-809 tablets.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline (Average of Screening and Day 0) in the Average TMC Scores From Weeks 9 & 12	Total TMC score is a sum of chorea scores which range 0-28, with a decrease indicating improvement in chorea	Screening, Day 0, Weeks 9, 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Success at the End of Therapy as Measured by the Patient Global Impression of Change (PGIC)	A treatment success is defined as Much or Very Much Improved at the Week 12 visit. The PGIC is a 7-point Likert Scale, ranging from very much worse to very much improved	12 weeks
Number of Participants With Treatment Success at the End of Therapy Based on Clinical Global Impression of Change (CGIC)	A treatment success is defined as Much or Very Much Improved at the Week 12 visit. The PGIC is a 7-point Likert Scale, ranging from very much worse to very much improved. The clinician was asked to comment about the subject.	12 weeks
Change in the Short Form 36 Health Survey (SF-36) Physical Functioning Score (Based on Items 3a to 3j) From Baseline to Week 12	Change in the Short Form 36 Health Survey (SF-36) physical functioning score (based on items 3a to 3j) from Baseline to Week 12. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability.	Baseline, 12 weeks
Change in Berg Balance Test (BBT)	The Berg Balance Test (BBT) is a 14-item assessment of sitting, standing, transferring, and turning. Each task ranging from standing up from a sitting position, to standing on one foot each task is given a score of zero (unable) to four (independent), and the final measure is the sum of all of the scores.The scale range, which is 0-56, with higher scores indicating better balance/lower fall risk.	Baseline, 12 weeks

Collaborators and Investigators

• Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.

Publications and helpful links

General Publications

• Claassen DO, Carroll B, De Boer LM, Wu E, Ayyagari R, Gandhi S, Stamler D. Indirect tolerability comparison of Deutetrabenazine and Tetrabenazine for Huntington disease. J Clin Mov Disord. 2017 Mar 1;4:3. doi: 10.1186/s40734-017-0051-5. eCollection 2017.
• Rodrigues FB, Wild EJ. Huntington's Disease Clinical Trials Corner: February 2018. J Huntingtons Dis. 2018;7(1):89-98. doi: 10.3233/JHD-189001.
• Huntington Study Group, Frank S, Testa CM, Stamler D, Kayson E, Davis C, Edmondson MC, Kinel S, Leavitt B, Oakes D, O'Neill C, Vaughan C, Goldstein J, Herzog M, Snively V, Whaley J, Wong C, Suter G, Jankovic J, Jimenez-Shahed J, Hunter C, Claassen DO, Roman OC, Sung V, Smith J, Janicki S, Clouse R, Saint-Hilaire M, Hohler A, Turpin D, James RC, Rodriguez R, Rizer K, Anderson KE, Heller H, Carlson A, Criswell S, Racette BA, Revilla FJ, Nucifora F Jr, Margolis RL, Ong M, Mendis T, Mendis N, Singer C, Quesada M, Paulsen JS, Brashers-Krug T, Miller A, Kerr J, Dubinsky RM, Gray C, Factor SA, Sperin E, Molho E, Eglow M, Evans S, Kumar R, Reeves C, Samii A, Chouinard S, Beland M, Scott BL, Hickey PT, Esmail S, Fung WL, Gibbons C, Qi L, Colcher A, Hackmyer C, McGarry A, Klos K, Gudesblatt M, Fafard L, Graffitti L, Schneider DP, Dhall R, Wojcieszek JM, LaFaver K, Duker A, Neefus E, Wilson-Perez H, Shprecher D, Wall P, Blindauer KA, Wheeler L, Boyd JT, Houston E, Farbman ES, Agarwal P, Eberly SW, Watts A, Tariot PN, Feigin A, Evans S, Beck C, Orme C, Edicola J, Christopher E. Effect of Deutetrabenazine on Chorea Among Patients With Huntington Disease: A Randomized Clinical Trial. JAMA. 2016 Jul 5;316(1):40-50. doi: 10.1001/jama.2016.8655.

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2013
• Primary Completion (Actual): December 5, 2014
• Study Completion (Actual): December 5, 2014

Study Registration Dates

• First Submitted: February 20, 2013
• First Submitted That Met QC Criteria: February 20, 2013
• First Posted (Estimate): February 21, 2013

Study Record Updates

• Last Update Posted (Actual): September 20, 2017
• Last Update Submitted That Met QC Criteria: August 22, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Huntington disease; Chorea; Tetrabenazine
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurocognitive Disorders; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Dyskinesias; Heredodegenerative Disorders, Nervous System; Dementia; Cognition Disorders; Huntington Disease; Chorea
• Other Study ID Numbers: SD-809-C-15